Highly stereoselective acid-catalyzed homonucleophilic substitution reactions.

Abstract

Enantiomeric 3-O-methyltemazepam and 3-O-ethyltemazepam were highly stereoselectively substituted by the 3-methoxy group of methanol in acidic anhydrous methanol and by the 3-ethoxy group of ethanol in acidic anhydrous ethanol, respectively. The stereoselectivity of the homonucleophilic substitution reactions was determined by circular dichroism spectropolarimetry and gas chromatography-mass spectrometry. In anhydrous solutions containing 0.5 M D2SO4 at 50 degrees C, for example, the stereoselectivity was approximately 63:1 for enantiomeric 3-O-methyltemazepam in CD3OD and approximately 94:1 for enantiomeric 3-O-ethyltemazepam in C2D5OD. The high stereoselectivity at C3 position was primarily due to the presence of a methyl group at N1 position.